Peptide antibiotics and their complexes with metal ions

Metal ions are essential for numerous antibiotics. They play a crucial role in the mechanism of action and may be involved in specific interactions with cell membrane or target molecules, such as: proteins and nucleic acids. Due to the fact that complexes usually poses a higher positive charge than free ligands, they might interact more tightly with DNA and RNA molecules. However, complexes may also form during antimicrobial agents application, because a lot of them possess functional groups which can bind metal ions present in physiological fluids. Many recent studies support a hypothesis that drugs may alter the serum metal ions concentration. Moreover, it has been shown that numerous complexes with antibiotics can cause DNA degradation, e.g. bleomycin which form stable complexes with redox metal ions and split the nucleic acids chain via the free radicals mechanism. Therefore, it is widely used in cancer therapy

Antitumoral, Antihypertensive, Antimicrobial, and Antioxidant Effects of an Octanuclear Copper(II)-Telmisartan Complex with an Hydrophobic Nanometer Hole

A new Cu(II) complex with the antihypertensive drug telmisartan, [Cu8Tlm16].24H2O (CuTlm), was synthesized and characterized by elemental analysis and electronic, FTIR, Raman and EPR spectroscopy. The crystal structure (at 120 K) was solved by X-ray diffraction methods. The octanuclear complex is a hydrate of but otherwise isostructural to the previously reported [Cu8Tlm16] complex. [Cu8Tlm16].24H2O crystallizes in the tetragonal P4/ncc space group with a=b=47.335(1), c=30.894(3) Å, Z=4 molecules per unit cell giving a macro-cyclic ring with a double helical structure. The Cu(II) ions are in a distorted bi-pyramidal environment with a somewhat twisted square basis, cis-coordinated at their core N2O2 basis to two carboxylate oxygen and to two terminal benzimidazole nitrogen atoms. Cu8Tlm16 has a toroidal-like shape with a hydrophobic nanometer hole and their crystal packing defines nano-channels that extend along the crystal c-axis. Several biological activities of the complex and the parent ligand were examined in vitro. The antioxidant measurements indicate that the complex behaves as a superoxide dismutase mimics with improved superoxide scavenger power as compared with native sartan. The capacity of telmisartan and its copper complex to expand human mesangial cells (previously contracted by angiotensin II treatment) is similar to each other. The antihypertensive effect of the compounds is attributed to the strongest binding affinity to angiotensin II type 1 receptor and not to the antioxidant effects. The cytotoxic activity of the complex and that of its components was determined against lung cancer cell line A549 and three prostate cancer cell lines (LNCaP, PC-3 and DU 145). The complex displays some inhibitory effect on the A549 line and a high viability decrease on the LNCaP (androgen-sensitive) line. From flow cytometric analysis it was established an apoptotic mechanism for the latter cell line. Telmisartan and CuTlm show antibacterial and antifungal activities in various strains and CuTlm displays improved activity against the Stafilococcus aureus strain as compared with unbounded copper(II).Fil: Islas, María Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; ArgentinaFil: Martínez Medina, Juan José. Universidad Nacional del Chaco Austral; ArgentinaFil: López Tévez, Libertad Leonor. Universidad Nacional del Chaco Austral; ArgentinaFil: Rojo, Teófilo. Universidad del País Vasco; EspañaFil: Lezama, Luis. Universidad del País Vasco; EspañaFil: Griera Merino, Mercedes. Universidad de Alcalá; EspañaFil: Calleros, Laura. Universidad de Alcalá; EspañaFil: Cortés, María Alicia. Universidad de Alcalá; España. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rodriguez Puyol, Manuel. Universidad de Alcalá; EspañaFil: Echeverría, Gustavo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Piro, Oscar Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Ferrer, Evelina Gloria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; ArgentinaFil: Williams, Patricia Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentin